Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/16—Inorganic salts, minerals or trace elements
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/17—Amino acids, peptides or proteins
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/17—Amino acids, peptides or proteins
  • A23L33/185—Vegetable proteins
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
  • A61K33/08—Oxides; Hydroxides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/42—Phosphorus; Compounds thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
  • A61K38/168—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/12—Drugs for disorders of the urinary system of the kidneys
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P19/00—Drugs for skeletal disorders
  • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
  • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/02—Nutrients, e.g. vitamins, minerals
• • G—PHYSICS
  • G06—COMPUTING; CALCULATING OR COUNTING
  • G06F—ELECTRIC DIGITAL DATA PROCESSING
  • G06F17/00—Digital computing or data processing equipment or methods, specially adapted for specific functions
  • G06F17/10—Complex mathematical operations

Definitions

• the present disclosure generally relates to health and nutrition. More specifically, the present disclosure relates to nutritional compositions having the potential to reduce metabolic acid load and methods of making and using the nutritional compositions to optimize and provide improved patient health, especially in individuals receiving long term tube feeding.
• Nutritional compositions can be targeted toward certain consumer types, for example, young, elderly, athletes, and also those suffering from chronic or acute conditions or illnesses, etc., based on the specific ingredients of the nutritional composition.
• Nutritional compositions can also be formulated based on the certain physiological conditions that the nutritional compositions are intended to manage, treat or improve.
• One goal of nutritional support is to improve metabolic disturbances in patients that may result from inactivity, a lack of variety in their diets or conditions which result in insufficiency in function of key organs. For example, patients who receive long-term tube-fed formulations often remain on a single dietary source for weeks, months or even years. As a result, the acid-base potential of the diet can play a significant role on the patient's health. Because tube fed patients are restricted in their dietary selections, and they may have renal insufficiency, the opportunity exists to positively influence acid-base balance through selective and targeted nutritional support.
• Patients may require specific nutritional compositions to prevent acid-base imbalance and for better management of their condition and/or to prevent onset of other chronic diseases (e.g., low bone mineral density, osteoporosis, skeletal muscle atrophy).
• Specific health benefits of improved acid-base balance through application of nutritional formulations include maintenance of bone, skeletal muscle and immune health, as well as improved pulmonary function.
• Improved acid-base balance through application of nutritional formulations may also include prevention of renal insufficiency and modulation of overt kidney disease. It is estimated that excess calciruia from excess diet acid load is 66 mg/day. If this calcium loss estimated from short term studies were extrapolated over time without adaptation a continuous loss of 66 mg/d would lead to 24 g per year or 480 g over 20 years.
• Individuals expected to derive benefit from the application of the present disclosure include, for example, patients receiving long term tube feeding. Such individuals may include patients suffering from Alzheimer's, dementia, cognitive impairment and/or other neurodegenerative disorders including, for example, cerebral palsy, amyotrophic lateral sclerosis, and general neurological impairment. Individuals who are long term tube fed may experience formula-driven issues since many current tube feeding formulas lead to a range of complications including, for example, low grade acidosis.
• Individuals expected to derive benefit from the application of the present disclosure may also include, for example, acutely ill individuals with renal compromise, elderly who are at risk of or experiencing musculoskeletal health problems, individuals in home care, bed-ridden persons, obese, obese with sleep apnea, individuals in a weight loss program trying to maintain lean body mass, pregnant women with elevated blood pressure, individuals with reduced respiration or respiratory capacity (including mechanically ventilated patients), individuals with metabolic or respiratory acidosis, diabetics including gestational diabetes, pediatrics with reduced renal and/or pulmonary function.
• respiratory insufficiencies may include, for example, chronic obstructive pulmonary disease (“COPD”), chronic ventilation, congestive heart failure (“CHF”), emphysema, and respiratory failure caused by, for example, disease, trauma, brain damage, etc.
• COPD chronic obstructive pulmonary disease
• CHF congestive heart failure
• emphysema respiratory failure caused by, for example, disease, trauma, brain damage, etc.
• renal insufficiencies include, but are not limited to, diabetes type 1 and 2, metabolic syndrome, aging, systemic lupus erythematosus, collagen diseases, renal damage, chronic dialysis, end stage renal disease, etc.
• TPN total parenteral nutrition
• EN Enteral nutrition
• Patients subject to other sole liquid food diets may also benefit from the application of the present disclosure.
• Such patients include, for example, the elderly and individuals attempting to lose weight by consuming solely liquid products designed to restrict caloric intake, while providing the nutrients required by the body.
• An example of such a full meal replacement liquid product includes Nestle " S.A.'s OPTIFAST®.
• IV intravenous
• oral routes can also lead to acidosis.
• patient populations receiving such IV or oral drugs may also benefit from the application of the present disclosure.
• Osteoporosis is a major public health threat characterized by low bone mass and fragility leading to increased risk of fractures. Osteoporosis affects an estimated 44 million Americans, or 55 percent of the people 50 years of age and older. To combat this debilitating disease, the public is advised to limit their protein, caffeine, phosphorus, and sodium intake based o the hypothesis that these factors adversely affect calcium metabolism. However, the basis of this advice, especially for protein and phosphorus, is controversial and the subject of much debate. Recent data show effects of protein and phosphorus to be opposite to what is predicted by the Remer and Manz calculations.
• Methods of formulations to decrease the acid load of nutritional composition are provided.
• Methods of making and using the nutritional compositions are also provided and include, for example, tube feed formulations, oral nutritional formulations, and modular formulations delivering low acid ash content.
• PRAL potential renal acid load
• the present disclosure includes increases in the cations Ca, Mg, plus P as the tools for increasing alkalinity of the diets.
• Another method used to estimate net acid production is the protein to Potassium ratio. Increased values correlated with measures of renal net acid excretion ("RNAE").
• the nutritional compositions include a source of protein.
• the protein source may be dietary protein including, but not limited to animal protein (such as milk protein, meat protein or egg protein), vegetable protein (such as soy protein, wheat protein, rice protein, canola and pea protein), or a combination thereof.
• the protein is selected from the group consisting of pea, whey, chicken, corn, caseinate, wheat, flax, soy, carob, canola, pea or combinations thereof.
• the nutritional compositions include a source of carbohydrates.
• Any suitable carbohydrate may be used in the present nutritional compositions including, but not limited to, sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrin, modified starch, amylose starch, tapioca starch, corn starch, isomalt, isomaltulose, or combinations thereof.
• the nutritional compositions include a source of fat.
• the source of fat may include any suitable fat or fat mixture.
• the fat source may include, but is not limited to, vegetable fat (such as olive oil, corn oil, sunflower oil, rapeseed oil, hazelnut oil, soy oil, palm oil, coconut oil, canola oil, lecithins, and the like) and animal fats (such as milk fat), structured lipids or other modified fats such as medium chain triglycerides.
• the nutritional composition further includes one or more prebiotics and/or fiber (soluble and/or insoluble).
• a "prebiotic” is preferably a food substance that selectively promotes the growth of beneficial bacteria or inhibits the growth or mucosal adhesion of pathogenic bacteria in the intestines.
• Prebiotics are not digested in the stomach and/or upper intestine or absorbed in the GI tract of the person ingesting them, but they are fermented by the gastrointestinal microflora and/or by probiotics.
• Prebiotics are for example defined by Glenn R. Gibson and Marcel B. Roberfroid, "Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics," J.
• the prebiotic can be acacia gum, alpha glucan, arabinogalactans, arabinoxylans, beta glucan, dextrans, fructooligosaccharides, galactooligosaccharides, galactomannans, gentiooligosaccharides, glucooligosaccharides, guar gum, inulin, isomaltooligosaccharides, lactosucrose, lactulose, levan, maltodextrins, partially hydrolyzed guar gum, pecticoligosaccharides, resistant starches, retrograded starch, soy oligosaccharides, sugar alcohols, xylooligosaccharides, or their hydrolysates, or combinations thereof.
• Prebiotics are useful in the present compositions to enhance the uptake of cations (alkaline-ash minerals) as a result of short chain fatty acids produced during prebiotic fermentation.
• the nutritional composition further includes one or more probiotics.
• probiotic micro-organisms are preferably microorganisms (alive, including semi-viable or weakened, and/or non-replicating), metabolites, microbial cell preparations or components of microbial cells that could confer health benefits on the host when administered in adequate amounts, more specifically, that beneficially affect a host by improving its intestinal microbial balance, leading to effects on the health or well-being of the host. See, Salminen S, Ouwehand A. Benno Y. et al "Probiotics: how should they be defined," Trends Food Sci. Technol. 1999: 10 107-10.
• micro-organisms inhibit or influence the growth and/or metabolism of pathogenic bacteria in the intestinal tract.
• the probiotics may also activate the immune function of the host. For this reason, there have been many different approaches to include probiotics into food products.
• the probiotic can be of bacterial, yeast, or fungal origin, including Saccharomyces, Debaromyces, Candida, Pichia, Torulopsis, Aspergillus, Rhizopus, Mucor, Penicillium, Bifidobacterium, Bacteroides, Clostridium, Fusobacterium, Melissococcus, Propionibacterium, Streptococcus, Enterococcus, Lactococcus, Staphylococcus, Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus, Lactobacillus or a combination thereof.
• the nutritional composition further includes one or more amino acids.
• the amino acid can be lsoleucine. Alanine. Leucine. Asparagine, Lysine, Aspartate, Methionine, Cysteine, Cystine, Phenylalanine, Glutamate, Threonine, Glutamine, Tryptophan. Citrulline, Glycine. Valine, Proline, Serine, Tyrosine, Arginine. Histidine or a combination thereof.
• the nutritional composition further includes one or more vitamin K 2 (menaquinone), synbiotics, fish oils, phytonutrients and/or antioxidants.
• the antioxidants can be, for example, vitamin A, carotenoids, vitamin C, vitamin E, selenium, flavonoids, Lactowolfberry, wolfberry, polyphenols, lycopene, lutein, lignan, coenzyme Q10 ("CoQI O") and glutathione.
• the nutritional composition includes minerals in a form that promotes metabolic alkalinity versus acidity; attached to various organic acids, amino or fatty acids, or naturally occurring as part of a real food.
• different forms of magnesium include: magnesium hydroxide (H 2 Mg0 2 ), magnesium phosphate tribasic (Mg 3 (P0 4 ) 2 ), magnesium oxide (MgO), magnesium oleate (C 36 H 66 Mg0 4 ).
• the nutritional composition may further include free coenzyme A, free carnitine, and combinations thereof.
• the nutritional composition includes free carnitine.
• the nutritional composition is in an administrable form such as pharmaceutical formulations, nutritional formulations, tube-feed formulations, dietary supplements, functional foods, beverage products or a combination thereof.
• the present disclosure provides methods of selecting a nutritional composition for administration to a patient.
• the methods include providing a protein selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, canola, pea or combinations thereof, and combinations of select minerals including, but not limited to, Mg, Ca, , and P.
• the methods include subtracting the base content from the acid content to obtain a PRAL value and selecting the nutritional composition for administration to the patient if the PRAL value is negative. Because we suspect that P is beneficial for the patient (but appears on the acid side of the PRAL equation), this nutrient will be accounted for separately.
• the final PRAL is reduced using minerals such as P, Ca, , and Mg.
• the present disclosure provides methods of administering a nutritional composition to a patient in need of same.
• the methods include providing a protein selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea, canola, cottonseed, .
• the methods also include subtracting the base content from the acid content to obtain a PRAL value, and administering the nutritional composition to the patient if the PRAL value is negative.
• the final PRAL is reduced using minerals such as P, Ca, , and Mg.
• a computer implemented processes for determining a PRAL value include providing a computer having an input device and a computer processor so constructed and arranged to calculate the metabolic acid potential of a nutritional composition using a modified PRAL equation to account for P and Na correctly.
• the protein is selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea or combinations thereof.
• the PRAL value is negative.
• the mineral content of the formulations is manipulated to reduce the PRAL.
• the present disclosure provides methods for preserving and/or preventing bone loss as well as skeletal muscle mass.
• the methods include providing a protein and combinations of select minerals (e.g., Mg, Ca, , P) selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea, canola, cottonseed, potato, rice, egg or combinations thereof, calculating an acid content of the nutritional composition using the modified PRAL equation.
• select minerals e.g., Mg, Ca, , P
• methods for buffering acidosis in a patient in need of same are provided.
• the methods include providing a protein selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, canola, pea or combinations thereof, calculating an acid content of a nutritional composition using the modified PRAL equation.
• An advantage of the present disclosure is to provide an improved tube feed formulation with net alkaline load that promotes renal health
• Yet another advantage of the present disclosure is to provide a nutritional composition that promotes bone health.
• Still yet another advantage of the present disclosure is to provide nutritional compositions that preserve skeletal muscle mass.
• Another advantage of the present disclosure is to provide a method of administering a nutritional composition.
• Another advantage of the present disclosure is to improve clinical patient outcomes, the functional mobility of patient and enhance the quality of life.
• Yet another advantage of the present disclosure is to provide a computer implemented process for determining a PRAL of a nutritional composition.
• FIG. 1 shows a graph demonstrating the relationship between net acid excretion (“NAE”) prediction and bone mineral density (“BMD”).
• NAE net acid excretion
• BMD bone mineral density
• the formula assigns sodium a protective role for calcium balance.
• sodium has been shown to compete with calcium for renal re-absorption and thus may impair calcium retention.
• Both salt- ' loading studies and reports of free-living populations find that urinary calcium excretion increases approximately 1 mmol (40 mg) for each 100 mmol (2300 mg) increase in dietary sodium in normal adults.
• the nutritional compositions and formulations of the present disclosure do not increase sodium content to increase alkalinity of a consumer's diet.
• the benefits of increased phosphate may be particularly beneficial for severely ill patients who are characterized by increased risk of infection as a result of metabolic alterations resulting from the inflammatory response.
• the host status dictates the response and virulence of microbes.
• Low intestinal concentrations of phosphate have been shown to turn on microbial virulence, while high phosphate turns off quorum sensing, or intercellular signaling between microbes.
• Extracellular phosphate has been shown to be depleted following acute surgical injury. Intestinal phosphate levels play a role in risk for infection in critically ill patients. See, Long et al., "Depletion of Intestinal Phosphate following Surgical Injury Activates the Virulence of P.
• dietary phosphate, or a phosphate analog is found to play a role in increasing extracellular phosphate levels or intestinal concentrations of phosphate, then a nutritional formulation with increased protein and therefore increased dietary phosphate levels may have a dual benefit for bone health as well as decreasing infection risk in severely ill patients.
• NAE Net Acid Excretion
• foods can be categorized as either net acidic versus net alkaline producing.
• “acid-ash” and “alkaline-ash” diets have been traditionally defined as the balance between anions (CI, P, S) and cations (Na, , Mg, Ca).
• CI, P, S anions
• cations Na, , Mg, Ca
• increased P has been shown to reduce urinary calcium loss.
• the acid-ash diet, or more acid producing diet has an excess of anions over cations (and vice versa for the alkaline-ash diet).
• acid producing diets have been found to negatively impact musculoskeletal and immune health.
• Some individuals may receive all or part of the nutritional requirements from formulated or synthetic diets. Dietary intake may include 50- 100% of their nutrient needs through supplemental formulas, where the range may be oral or tube feeding.
• Reasons for partial to complete supplementation of the diet with specialized formulas include institutional or home care and conditions such as chronic obstructive pulmonary (“COPD”) patients who have difficulty consuming an adequate diet as a result of their physical and/or psychological limitations (e.g., fatigue, fear of choking or suffocation during chewing or swallowing, and increased energy needs); patients having undergone major surgery, whose energy and protein needs are increased and are unable to ingest adequate protein or nutrients with a normal diet; individuals suffering from a neuromuscular disease, such as Amyotrophic Lateral Sclerosis (“ALS”), where the majority of the diet may come from supplementation with tube feeding and oral intake is reserved for pleasure; ageing care patients that have dietary restrictions or physical, economic or social conditions that limit their ability to consume an adequate diet; pediatric patients, such as cyst
• Acid [(P x 0.0366) + (Protein (g/day) x 0.4888) + (CI x 0.0268)]
• Base [(Ca x 0.0125) + (Mg x 0.0263) + (K x 0.021 1 ) + ( a x 0.0413)]
• P is the phosphorous content of the foodstuff (mg/day)
• CI is the chloride content of the foodstuff (mg/day)
• Ca is the calcium content of the foodstuff (mg/day)
• Mg is the magnesium content of the foodstuff (mg/day)
• K is the potassium content of the foodstuff (mg/day)
• Na is the sodium content of the foodstuff (mg/day).
• Values for the variables in the equations may be obtained, for example, from any commercial dietary analysis software program such as, for example, Food Processor by ESHA Research or Nutritionist ProTM Diet Analysis by Axxya Systems LLC.
• the single largest contributor to the acid-base potential of the nutritional composition is protein, but the generic term "protein” does not distinguish between the different sources of protein, which can have very different impacts on the diet's acid-base balance. These differences have not previously been accounted for in equations used for predicting acid influence of compositions after metabolism. Indeed, the "protein” in the Remer and Manz equation is simply the amount of protein in the composition, regardless of the type of protein used or whether a mixture of different proteins was used.
• Alexy et al. reported a correlation between high dietary PRAL and lower cortical area and bone mineral content in children. See, Alexy U, et al., "Long-term protein intake and dietary potential renal acid load are associated with bone modeling and remodeling at the proximal radius in healthy children," Am. J. Clin. Nutr,, 82: 1 107-1 1 14 (2005). Additionally, young girls consuming high amounts of fruits, an alkaline producing food, had high heel bone mineral density. See, McGartland CP, et al., “Fruit and vegetable consumption and bone mineral density: the Northern Ireland Young Hearts Project," Am. J. Clin. Nutr., 80: 1019-1023 (2004).
• NAE physiological measurement
• the cell energy charge has been proposed as an important control for the cell to favor either anabolic or catabolic processes. Metabolic stress, nutritional stress, or both may result in a loss of nucleotides from the adenylate pool and become conditionally essential under these conditions.
• the maintenance of the cell energy charge can attenuate the upregulation of catabolic processes resulting from metabolic stress, nutritional stress, or both which includes protein breakdown.
• ubiquitin which functions to regulate protein turnover in a cell by closely regulating the degradation of specific proteins
• calpain the calpain family of proteases consists of 3 well- characterized proteins, ⁇ -calpain, m-calpain and calpastatin
• lysosomal organelles containing digestive enzymes.
• AMP Protein Kinase AMPK
• PCr'VCr phosphocreatine/creatine
• metabolic acidosis has been described for its association with skeletal muscle wasting in several different conditions (e.g., chronic renal failure; obese on weight loss diets) and has been the subject of review. See, Caso G, et al., "Control of muscle protein kinetics by acid-base balance," Curr. Opin. Clin. Nutr. Metab. Care, 8:73-76 (2005).
• skeletal muscle proteolysis appears to be an adaptive response. Glutamine breakdown from skeletal muscle is a substrate for ammonia which can accept protons and possibly reduce acidosis.
• Ammonium liberated during glutamine deamination facilitates the excretion of acids by accepting a proton which may help to minimize acidosis.
• Glutamine has other roles in the body.
• One is as a precursor of arginine via citrulline.
• the addition of exogenous citrulline may spare muscle protein breakdown since citrulline may conserve glutamine and allow for more glutamine to serve as a proton acceptor.
• This diagram shows how the addition of citrulline can block the conversion of ornithine to citrulline. Additionally with citrulline present to serve as the precursor to arginine, the higher level of arginine would also allow for a larger portion of the ornithine to come from arginine and not glutamine.
• urinary potassium excretion (a marker of dietary potassium intake) was correlated to percent of lean body mass. See, Dawson-Hughes et al., "Alkaline diets favor lean tissue mass in older adults," Am. J. Clin. Nutr., Mar;87(3):662-5 (2008). It was concluded that this nitrogen sparing is "potentially sufficient to both prevent continuing age-related loss of skeletal muscle mass and restore previously accrued deficits.” Id.
• compositions may also support renal health, which can be negatively influenced by metabolic acidosis (chronic or acute). Specifically, metabolic acidosis can influence hormones that control fluid balance in the body. Fluid balance is also responsible for mineral excretion (electrolytes) that are key in maintenance of acid-base balance.
• metabolic acidosis can influence hormones that control fluid balance in the body. Fluid balance is also responsible for mineral excretion (electrolytes) that are key in maintenance of acid-base balance.
• acidosis dietary glutamine and dietary citrulline may be used. With respect to glutamine, for example, during a state of acute or chronic acidosis, skeletal muscle breakdown appears to be an adaptive response partly driven by the need for glutamine. See, Epler et al. "Metabolic acidosis stimulates intestinal glutamine absorption," J.
• Glutamine available for proton quenching comes from only two sources: the diet and the skeletal muscle. Chronic skeletal muscle catabolism is highly undesirable can lead to skeletal muscle atrophy. Glutamine quenches protons (hydrogen) that may be upset in conditions such as chronic obstructive pulmonary disease and renal insufficiency caused by ageing or disease.
• Alkaline diets may also be used to offset respiratory insufficiency, as discussed above.
• ICU Intensive Care Unit
• patients often require artificial respiration. This condition results in proton build up because the individuals cannot naturally increase their breathing rate to 'blow off excess carbon dioxide and protons and may lead to metabolic acidosis. Therefore, it would be beneficial to use glutamine in combination with the optimized alkaline formula compositions of the present disclosure for both tube feeding and parenteral administration. Indeed, correction of acidosis may help to preserve skeletal muscle mass and improve the health of patients with pathological conditions associated with acidosis. Additionally, patients in the ICU typically have a high demand for, but a low level of glutamine.
• a shunt of glutamine for correcting acidosis also contributes to immunosuppression as the glutamine supply to the enterocytes of the gut is reduced. Therefore, supplementing and correcting metabolic acidosis may also improve the patient's immune status.
• dietary citrulline may also be used as a buffer of "acidosis.”
• Citrulline has one less nitrogen than arginine and may be substituted for arginine.
• the oxidation of dietary fatty acids and hepatic desaturation/elongation of palmitic acid can occur to a greater degree in abdominally obese individuals. This increased oxidation may represent a compensatory mechanism to redirect fatty acids from incorporation into the liver to prevent liver fat accumulation.
• reduced levels of free coenzyme A and free carnitine may limit the carnitine-mediated transfer of long-chain fatty acids into mitochondria for oxidation.
• metabolic acidosis obese individuals may be more susceptible to liver fat accumulation whereas the present alkaline formula would seek to attenuate or minimize such a response. This metabolic improvement could improve the preservation of lean body mass.
• the nutritional compositions of the present disclosure may include free coenzyme A, free carnitine, or combinations thereof.
• the nutritional compositions include free carnitine.
• the nutritional compositions include from about 1 to about 220 mg of free carnitine per complete feed.
• the nutritional compositions include from about 100 to about 200 mg of free carnitine per complete feed.
• IGF-l insulin-like growth factor- 1
• IGFBPs insulin-like growth factor- 1 binding proteins
• the acid potential of the nutritional compositions of the present disclosure may be obtained by substituting the "Protein (g/day) x 0.4888" value in the Remer and Manz acid equation with "protein (g/day) x acid potential of the protein (mEq/l OOg protein)." Accordingly, the improved equation for determining PRAL values is as follows:
• Acid [(P x 0.0366) + (protein (g/day) x acid potential of the protein (mEq/l OOg protein)) + (CI x 0.0268)]
• P is the phosphorous content of the foodstuff (mg/day)
• CI is the chloride content of the foodstuff (mg/day)
• Ca is the calcium content of the foodstuff (mg/day)
• Mg is the magnesium content of the foodstuff (mg/day)
• Na is the sodium content of the foodstuff (mg/day).
• the single largest contributor to the acid/base potential of a nutritional composition is protein due, at least in part, to the sulfur amino acid content, which varies with each different type of protein.
• the two primary amino acids that are found in proteins and which contain sulfur are methionine and cystine.
• methionine and cystine are the primary amino acids that are found in proteins and which contain sulfur.
• cystine is required to calculate the acid potential of each individual protein.
• molar amounts of each may be calculated using each respective molar mass.
• the molar mass of methionine is 149.2 g/mol and the molar mass of cystine is 240.3 g/mol.
• the molar amount of sulfur may then be calculated using the following equation:
• mmol Sulfur (mEq/diet) (mg methionine/149.2 g/mol) + (2 x (mg cystine/240.3 g/mol)).
• the acid potential of the protein is multiplied by 2.
• the acid potential of whey protein is calculated as follows:
• the acidity of blends of proteins can also be easily determined by the improved equation by using the fractional contribution of each protein source according to its sulfur amino acid content. Therefore, use of the improved equation allows for the preparation of nutritional compositions having several [0091] Further, from these calculations, it appears that lower PRAL diets (more alkaline producing versus more acid producing) may have beneficial effects on musculoskeletal, immune and renal health. Nestle's blenderized tube feeds, Compleat ® and Isosource ® Mix, already have a low calculated PRAL value. However, these formulas can be further optimized to deliver greater benefits.
• the long term use of these optimized tube feeds may be appropriate for the maintenance of bone, skeletal muscle mass and strength, and renal or pulmonary function.
• Populations expected to benefit include long-term home care patients, elderly, ICU patients, pediatric patients requiring medical nutrition, bed-ridden patients, chronic obstructive pulmonary disease (“COPD”) patients, ventilated patients, patients recovering from trauma, diabetic patients, hepatic patients, patients with renal insufficiency, etc.
• COPD chronic obstructive pulmonary disease
• the calculations for the modified equation may be performed manually by a user or generated automatically using a computer implemented process.
• computers having a processor can be used to estimate the acidity of the nutritional compositions.
• the processor should be so constructed and arranged to be able to calculate an acid component of the improved PRAL equation using the already cited modified PRAL equation.
• the improved modified equation of the present disclosure to make and/or use nutritional compositions provides several benefits.
• the improved equation and methods of using the equation accurately predict the physiological response to Phosphorus and Sodium in a patient's diet.
• the improved equations provide a user the ability to formulate a diet that minimizes the impact of acid/base potential of a patient's diet on the patient.
• consumption of the nutritional compositions derived via use of the improved equations provide resultant clinical benefits to the patient's musculoskeletal health including, but not limited to, preservation of lean body mass and bone mineral density.
• the term "nutritional composition” includes, but is not limited to, complete nutritional compositions, partial or incomplete nutritional compositions, and disease or condition specific nutritional compositions.
• a complete nutritional composition i.e., those which contain all the essential macro and micro nutrients
• Patients can receive 100% of their nutritional requirements from such complete nutritional composition.
• a partial or incomplete nutritional composition does not contain all the essential macro and micro nutrients and cannot be used as a sole source of nutrition for the patient.
• Partial or incomplete nutritional compositions can be used as a nutritional supplement.
• a disease or condition specific nutritional composition is a composition that delivers nutrients or pharmaceuticals and can be a complete or partial nutritional composition.
• the nutritional composition can be a complete feeding or an oral nutritional supplement.
• an "oral nutritional supplement” includes, but is not limited to, orally ingested formulations, enteral nutrition formulations and tube feeds.
• the nutritional composition can be in a formulation designed for any mammal such as a human or an animal.
• the key acid or base contributing ingredients in the nutritional composition can also be provided as a modular product.
• a modular product can be defined as a method of delivering one or more specific nutrients as a supplement and not intended to be used for sole source nutrition.
• the nutritional composition is in an administrable form selected from the group consisting of pharmaceutical formulations, nutritional formulations, tube-feed formulations, total parenteral nutrition formulations, enteral nutrition formulations, dietary supplements, functional foods and beverage products.
• a "tube feed” formulation is preferably a complete or incomplete nutritional product that is administered to an animal's gastrointestinal system, including but not limited to an oral access port, nasogastric tube, orogastric tube, gastric tube, jejunostomy tube (J- tube), percutaneous endoscopic gastrostomy (PEG), port, such as a chest wall port that provides access to the stomach, jejunum and other suitable access ports.
• an oral access port nasogastric tube, orogastric tube, gastric tube, jejunostomy tube (J- tube), percutaneous endoscopic gastrostomy (PEG), port, such as a chest wall port that provides access to the stomach, jejunum and other suitable access ports.
• J- tube jejunostomy tube
• PEG percutaneous endoscopic gastrostomy
• port such as a chest wall port that provides access to the stomach, jejunum and other suitable access ports.
• the nutritional compositions comprise a source of protein.
• the protein source may be dietary protein.
• the dietary protein is any suitable dietary protein including, but not limited to animal protein (such as milk protein, meat protein or egg protein), vegetable protein (such as soy protein, wheat protein, rice protein, and pea protein), or a combination thereof.
• animal protein such as milk protein, meat protein or egg protein
• vegetable protein such as soy protein, wheat protein, rice protein, and pea protein
• the protein is selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea, canola, cottonseed, potato, rice, egg or combinations thereof.
• the protein includes pea protein. Regardless of the protein source, the protein should have low acid potential.
• the PRAL value for a tube feed formulation is between about - 20 mEq and about -100 mEq. In another embodiment, the PRAL value for a tube feed formulation is between about -22 mEq and about -95 mEq. In another embodiment, the PRAL value for a tube feed formulation is between about -24 mEq and about -90 mEq. In another embodiment, the PRAL value for a tube feed formulation is between about -26 mEq and about - 85 mEq. In another embodiment, the PRAL value for a tube feed formulation is between about - 28 mEq and about -80 mEq.
• the PRAL value for a tube feed formulation is between about -29 mEq and about -75 mEq. In another embodiment, the PRAL value for a tube feed formulation is between about -30 mEq and about -70 mEq.
• the Protein: for a tube feed formulation is between 0.5 (g/mEq) to 1.25 (g/mEq). In another embodiment, the Protein. ratio is between 0.75 (g/mEq) to 1 .2 (g/mEq). In another embodiment, the Protein: ratio is between 0.9 (g/mEq) to 1 .1 (g/mEq).
• the protein is provided in effective amounts to result in nutritional compositions having large negative PRAL values.
• the protein is present in the nutritional compositions in amounts between about 1 g and about 200 g. In another embodiment, the protein is present in the nutritional composition in amounts between about 50 g and about 150 g.
• the nutritional compositions include pea protein.
• the nutritional compositions comprise a source of carbohydrates. Any suitable carbohydrate may be used in the present nutritional compositions including, but not limited to, sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrin, modified starch, amylose starch, tapioca starch, corn starch or combinations thereof.
• the nutritional compositions include a source of fat.
• the source of fat may include any suitable fat or fat mixture.
• the fat source may include, but is not limited to, vegetable fat (such as olive oil, corn oil, sunflower oil, rapeseed oil, hazelnut oil, soy oil, palm oil, coconut oil, canola oil, lecithins, and the like) and animal fats (such as milk fat).
• the nutritional composition further includes one or more prebiotics and/or fiber (soluble and/or insoluble).
• a prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microbiota, that confers benefits upon host well-being and health.
• Non-limiting examples of prebiotics include fructooligosaccharides, inulin, lactulose, galactooligosaccharides, acacia gum, soyoligosaccharides, xylooligosaccharides, isomaltooligosaccharides, arabinoxylans, gentiooligosaccharides, lactosucrose, glucooligosaccharides, pecticoligosaccharides, resistant starches, sugar alcohols or combinations thereof.
• the nutritional composition further includes one or more probiotics.
• probiotic micro-organisms are preferably microorganisms (alive, including semi-viable or weakened, and/or non-replicating), metabolites, microbial cell preparations or components of microbial cells that could confer health benefits on the host when administered in adequate amounts, more specifically that beneficially affect a host by improving its intestinal microbial balance, leading to effects on the health or well-being of the host.
• probiotics are preferably microorganisms (alive, including semi-viable or weakened, and/or non-replicating), metabolites, microbial cell preparations or components of microbial cells that could confer health benefits on the host when administered in adequate amounts, more specifically that beneficially affect a host by improving its intestinal microbial balance, leading to effects on the health or well-being of the host.
• the probiotics may also activate the immune function of the host.
• probiotics include Saccharomyces, Debaromyces, Candida, Pichia, Torulopsis, Aspergillus, Rhizopus, Mucor, Penicillium, Bifidobacterium, Bacteroides, Clostridium, Fusobacterium, Melissococcus, Propionibacterium, Streptococcus, Enterococcus, Lactococcus, Staphylococcus, [00107]
• the nutritional composition further includes one or more amino acids.
• Non-limiting examples of amino acids include Isoleucine, Alanine, Leucine, Asparagine, Lysine, Aspartate, Methionine, Cysteine, Cystine, Phenylalanine, Glutamate, Threonine, Glutamine, Tryptophan, Citrulline, Glycine, Valine, Proline, Serine, Tyrosine, Arginine, Histidine or combinations thereof.
• the nutritional composition further includes one or more synbiotics, fish oils, and/or phytonutrients.
• a synbiotic is a supplement that contains both a prebiotic and a probiotic that work together to improve the microflora of the intestine.
• fish oils include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
• phytonutrients include those that are flavonoids and allied phenolic and polyphenolic compounds, terpenoids such as carotenoids, and alkaloids including, for example, quercetin, curcumin, limonin, or combinations thereof.
• the nutritional composition further includes antioxidants.
• Antioxidants are molecules capable of slowing or preventing the oxidation of other molecules.
• Non-limiting examples of antioxidants include vitamin A, carotenoids, vitamin C, vitamin E, selenium, flavonoids, Lactowolfberry, wolfberry, polyphenols, lycopene, lutein, lignan, coenzyme Q10 (CoQI O), glutathione or combinations thereof.
• the present disclosure provides methods of selecting a nutritional composition for administration to a patient.
• the methods include providing a protein selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea or combinations thereof, calculating an acid content of the nutritional composition using the modified, PRAL equation.
• the present disclosure provides methods of administering a nutritional composition to a patient in need of same.
• the methods include providing a protein selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea, canola, cottonseed, potato, rice, egg or combinations thereof, calculating an acid content of the nutritional composition using the modified PRAL equation.
• the present disclosure provides methods for treating and/or preventing bone loss and methods of preserving skeletal muscle mass.
• the methods include providing a protein selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea or combinations thereof, calculating an acid content of the nutritional composition using the equation.
• methods for buffering acidosis in a patient in need of same include providing a protein selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, carob, pea or combinations thereof and manipulating the P and other cations (Mg, Ca, ) to achieve alkaline load.
• the improved equation and compositions and methods derived from same provide methods of predicting acidity (acid-ash content) of nutritional compositions or diets in order to precisely determine the alkalinity effect of protein and blends of protein in combination with minerals on the skeletal muscle, bone and immune health of patients consuming same.

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